WNT pathway alteration is related to dysplastic cortical tissue and not to adjacent tissue of patients with FCD and refractory epilepsy

Background Focal cortical dysplasia (FCD) is a malformation of the cortical development that cause medical refractory seizures and the only treatment may be surgical resection of the affected area of the brain. People affected by FCD may present seizures of variable severity since childhood. The physiopathology of the disease is not yet understood, however it is known that several genes alterations may play their role. The WNT/β-catenin pathway is associated with cell transformation and migration and for this reason may be crucial for understanding FCD’s aetiology. The aim of this study was to explore genes related to the WNT/β-catenin pathway in patients with FCD type II. Methods Dysplastic tissue and tissue adjacent to the primary dysplastic lesion of patients with FCD type II were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array containing 84 genes related to the WNT pathway. Results In patient 1, the analysis showed a difference in the expression of seven genes, demonstrating an increase in AXIN2, FRAT2, FZD9, KREMENI and PP2R1A genes and a reduction in CSNK1G3 and PPP2CA genes in dysplastic tissue. In patient 2, the analysis showed increased expression of CSNK1A1, FZD4 and PPP2CA genes, as well as reduced of CTNNBIP1 gene in dysplastic tissue. Conclusion Dysregulation in the expression of genes that control the receptors of the WNT pathway keeps it in an inactivated state. Therefore, a eventual manipulation of this pathway focusing on its activation may influence molecular manifestations underlying the epileptogenic status in injured brain tissue, which could act as a therapeutic alternative to FCD type II. The WNT/ β-catenin signaling pathway is crucial for the control of embryonic development, which takes place through the regulation of cell differentiation, migration and proliferation, and apoptosis process.

Livin/BIRC7 gene expression as a possible diagnostic biomarker for endometrial hyperplasia and carcinoma

Background Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family which are implicated in development of cancer through the inhibition of apoptosis process. This case-control study was intended to investigate livin/BIRC7 gene expression in endometrial hyperplasia and carcinoma and its correlation to some oxidative stress markers in addition to its possible diagnostic performance. Methods This study included 90 participants [30 endometrial hyperplasia patients, 30 endometrial carcinoma patients, and 30 healthy controls]. Livin/BIRC7 gene expression was analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Serum catalase activity was assessed by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde level was measured by the colorimetric method. Results Livin/BIRC7 gene expression was significantly (p < 0.001) higher in endometrial carcinoma from patients with endometrial hyperplasia when compared to controls. A positive correlation was found between livin/BIRC7 expression and serum catalase activity and malondialdehyde level in endometrial hyperplasia and carcinoma. The detection of livin/BIRC7 in endometrial carcinoma has excellent sensitivity and specificity. Conclusions Livin/BIRC7 was overexpressed in endometrial carcinoma with excellent power to differentiate endometrial carcinoma from endometrial hyperplasia or healthy subjects, suggesting that it might be a useful molecular marker for endometrial carcinoma diagnosis.

Current Biomarkers of Apoptosis Process in Chronically Inflamed Nasal Sinus Epithelium: Representatives of BAX, Bcl-2 and miRNA Group

In chronic upper respiratory tract diseases, increased cell proliferative activity is observed, which is coordinated by Bcl-2 proteins as well as by small non-coding RNAs.The aim of this study was to determine the expression of critical apoptosis markers at the mRNA and miRNA level in patients with chronic rhinosinusitis with nasal polyps (CSRwNP).The study group consisted of 10 patients with CSRwNP and 10 healthy controls. TUNEL staining was performed to detect in situ apoptosis in the maxillary sinus mucosa. The levels of selected mRNA transcripts associated with cell survival and apoptosis: BAX, p53, p21, CASP3, CASP9, c-MYC, CCND1, BRIC5 and APAF1 and miRNAs: miR-17-5p, miR-145-5p, miR-146a-5p and miR-203a-3p were determined by RT-qPCR. CSRwNP patients showed increased apoptosis determined by TUNEL assay accompanied by increased expression of BAX, P21, P53, CASP3, CASP9, c-MYC, APAF-1 transcripts and decreased mRNA levels of BCL-2 and BIRC5. There were increased expression levels of miR-203a-3p and decreased expression levels of miR-17-5p and miR-145-5p. These findings appear to be characteristic features of apoptosis in CRSwNP. The proapoptotic effect of miR-203a-3p may be crucial for future treatment strategies for CRSwNP.

Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

Endometriosis (EMS) remains, to date, an intriguing and debilitating gynecological disorder that possesses a multifactorial substrate. Recent studies with the objective of elucidating its etiology highlighted the antagonistic effect of EMS on a multiple of processes involved in homeostasis. Although the current oxidative biomarkers clearly reveal the consequences induced by EMS, its implication in the associated inflammatory reactions could be much more complex. Besides the overproduction of reactive oxygen species (ROS) that leads to an exacerbated oxidative response, it also changes the normal expression of several pro-inflammatory modulators, reflected by the fluctuating activity of several pro- and anti-apoptotic mediators whose expression is impaired. In light of this topic, several studies elucidate the involvement of apoptosis in EMS, being brought controversial findings, even reports with no significant change. Further, some authors reported an abnormal expression of multiple genes that are crucial for the overall functionality of the female reproductive system. Cumulatively, it seems that the subsequent oxidative imbalance and apoptosis process impairment could further disrupt the normal removal of unnecessary biological products. Based on all gathered evidence, we could argue that the related stress state could determine human endobiota impairment, which could further participate in the inflammatory and main antioxidant enzyme changes occurring in EMS. Moreover, a correlation between endobiota integrity, inflammation, and oxidative stress (OS) was suggested in relation to the possible predisposition to pathogen determined infections.

RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.

Effects of Silver Nanoparticles on Proliferation and Apoptosis in Granulosa Cells of Chicken Preovulatory Follicles: An In Vitro Study

The continuous development of poultry production related to the growing demand for eggs and chicken meat makes it necessary to use modern technologies. An answer to this demand may be the use of nanotechnology in poultry farming. One of the promising nanomaterials in this field are silver nanoparticles (AgNPs), which are used as disinfectants, reducing microbial pollution and the amounts of greenhouse gases released. This study aimed to evaluate the effect of AgNPs on the proliferation and apoptosis process in the granulosa cells of chicken preovulatory follicles. The in vitro culture experiment revealed that both 13 nm and 50 nm AgNPs inhibited the proliferation of the granulosa cells. However, a faster action was observed in 50 nm AgNPs than in 13 nm ones. A size-dependent effect of AgNP was also demonstrated for the caspase-3 activity. AgNPs 13 nm in size increased the caspase-3 activity in granulosa cells, while 50 nm AgNPs did not exert an effect, which may indicate the induction of distinct cell death pathways by AgNPs. In conclusion, our study reveals that AgNPs in vitro inhibit granulosa cell proliferation and stimulate their apoptosis. These results suggest that AgNPs may disrupt the final stage of preovulatory follicle maturation and ovulation.

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

Nucb2 is a multifunctional protein associated with a variety of biological processes. Multiple studies have revealed that Nucb2, and its derivative nesfatin-1, are involved in carcinogenesis. Interestingly, the role of Nucb2/nesfatin-1 in tumorigenesis seems to be dual—both pro-metastatic and anti-metastatic. The implication of Nucb2/nesfatin-1 in carcinogenesis seems to be tissue dependent. Herein, we review the role of Nucb2/nesfatin-1 in both carcinogenesis and the apoptosis process, and we also highlight the multifaceted nature of Nucb2/nesfatin-1.

All-Fibre Label-Free Nano-Sensor for Real-Time in situ Early Monitoring of Cellular Apoptosis

The achievement of all-fibre functional nano-modules for subcellular label-free measurement has long been pursued due to the limitations of manufacturing techniques. In this paper, a compact all-fibre label-free nano-sensor composed of a fibre taper and zinc oxide nano-gratings is designed and applied for the early monitoring of apoptosis in single living cells. Because of its nanoscale dimensions, mechanical flexibility and minimal cytotoxicity to cells, the sensing module can be loaded in cells for long-term in situ tracking with high sensitivity. A gradual increase in the nuclear refractive index during the apoptosis process is observed, revealing the increase in molecular density and the decrease in cell volume. The strategy used in this study not only contributes to the understanding of internal environmental variations during cellular apoptosis but also provides a new platform for non-fluorescent all-fibre devices to investigate cellular events and to promote new progress in fundamental cell biochemical engineering.

Biochemical differences between nano- and normal formulation of tamoxifen and other natural bioactive materials ameliorate breast cancer in experimental rats

Background Human breast cancer is the most prevalent malignancy in women all-over the world. The aim is to look further into the effectiveness of the nanoformulation of tamoxifen and even certain bioactive compounds (yeast, isoflavone, and silymarin) and their impacts on diminishing the breast cancer progression. A single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) was administered intragastrically by fifty-four female Sprague–Dawley rats. After fourteen days of DMBA admission, the procedure protocol actually started out. At long last, all of the experimental findings assessed, tabulated, and statistically analyzed. Results In contrast to the normal groups, a substantial elevation in apoptosis and lipid peroxide was observed in all nanogroups. Conclusion The best biochemical outcome and beneficial factors which elevate the occurrence and activation of the apoptosis process have been demonstrated by nanotamoxifen.